Ned 19
目录号 : GC36713
Ned 19 是一种选择性膜透性非竞争性 NAADP 拮抗剂，抑制 NAADP 介导的 Ca2+ 信号传导，IC50 为 65 nM。 Ned 19 强烈抑制小鼠的肿瘤生长和血管形成以及肺转移。
Cas No.:874374-25-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ned 19 is a selective membrane-permeant non competitive NAADP antagonist and inhibits NAADP-mediated Ca2+ signaling, with an IC50 of 65 nM[1]. Ned 19 strongly inhibits tumor growth and vascularization as well as lung metastases in mice[2]. Ca2+
Ned 19 (25-100 μM; 24-72 hours) reduces cell proliferation[2]. Ned 19 (25-100 μM; 24-72 hours) reduces markedly the cell number[2]. Ned 19 (25-100 μM; 24-72 hours) reduces the S phase percentage and increases of the G0/G1 phase percentage evaluated by cell cycle analysis[2]. Ned 19 (25-100 μM; 24-72 hours) induces cell apoptosis a time-dependent manner[2]. Ned 19 (25-100 μM; 24-72 hours) reduces expression of N-cadherin and increases expression of E-cadherin, affecting the cell migratory behavior[2]. Cell Proliferation Assay[2] Cell Line: B16 cells
Ned 19 (i.p.; 5 mg/Kg/every second day; 4 week) impaires severely tumor growth[2]. Animal Model: Adult male C57BL/6 mice[2]
[1]. Rosen D, et al. Analogues of the nicotinic acid adenine dinucleotide phosphate (NAADP) antagonistNed-19 indicate two binding sites on the NAADP receptor. J Biol Chem. 2009 Dec 11;284(50):34930-4. [2]. Annarita Favia, et al. NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis. Sci Rep. 2016; 6: 18925.
| Cas No. | 874374-25-1 | SDF | |
| Canonical SMILES | OC(C(C1)NC(C2=CC=C(OC)C(CN3CCN(C4=CC=CC=C4F)CC3)=C2)C5=C1C6=C(N5)C=CC=C6)=O | ||
| 分子式 | C30H31FN4O3 | 分子量 | 514.59 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9433 mL | 9.7165 mL | 19.4329 mL |
| 5 mM | 0.3887 mL | 1.9433 mL | 3.8866 mL |
| 10 mM | 0.1943 mL | 0.9716 mL | 1.9433 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The Role of Two-Pore Channels in Norepinephrine-Induced [Ca2+]i Rise in Rat Aortic Smooth Muscle Cells and Aorta Contraction
Cells 2019 Sep 25;8(10):1144.PMID:31557916DOI:10.3390/cells8101144.
Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) isolated from rat aorta and on aorta contraction. To address this issue, the NAADP structural analogue and inhibitor of TPCs, Ned 19, was applied. We have demonstrated a high degree of colocalization of the fluorescent signals of cis-NED 19 and endolysosmal probe LysoTracker in SMCs. Both cis- or trans-NED 19 inhibited the rise of [Ca2+]i in SMCs induced by 100 μM NE by 50-60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 μM, respectively. The inhibition by Ned 19 stereoisomers of the effects of AngII, AVP, and 5-HT was much weaker. Both forms of Ned 19 caused relaxation of aortic rings preconstricted by NE, with relative potency of cis-NED 19 several times higher than that of trans-NED 19. Inhibition by cis-NED 19 of NE-induced contraction was maintained after intensive washing and slowly reversed within an hour of incubation. Cis- and trans-NED 19 did not cause decrease in the force of aorta contraction in response to Ang II and AVP, and only slightly relaxed aorta preconstricted by 5-HT and by KCl. Suppression of TPC1 in SMCs with siRNA caused a 40% decrease in [Ca2+]i in response to NE, whereas siRNA against TPC2 did not change NE calcium signaling. These data suggest that TPC1 is involved in the NE-stimulated [Ca2+]i rise in SMCs. Inhibition of TPC1 activity by Ned 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.